The potential to modulate the activity of the immune systemby
interventions with specific nutrients is termed immunonutrition.This
concept may be applied to any situation in which an alteredsupply of
nutrients is used to modify inflammatory or immuneresponses.
However, immunonutrition has become associated mostclosely with
attempts to improve the clinical course of criticallyill and
surgical patients, who will often require an exogenous supply of nutrients
through the parenteral or enteral routes.
Major surgery is followed by a period of immunosuppression that
increases the risk of morbidity and mortality due to infection.
Improving immune function during this period may reduce complications
due to infection. Critically ill patients are at greater riskof
adverse outcomes than surgical patients. In these patientscomplex
variable immune and inflammatory changes occur thatare only now
being well defined. A biphasic response with anearly
hyperinflammatory response followed by an excessive compensatory
response associated with immunosuppression is seen in manysuch
patients. Here, early treatment is aimed at decreasingthe
inflammatory response rather than enhancing it, to abrogatethe
hyperinflammation and prevent the compensatory immunosuppression.
Three potential targets exist for immunonutritionmucosalbarrier
function, cellular defence, and local or systemic inflammation.The
nutrients most often studied for immunonutrition are arginine,
glutamine, branched chain amino acids, n-3 fatty acids, and
nucleotides (an overview of their key functions and effectsappears
on bmj.com).15 Combinations of some or allof these
nutrients are present in commercially available enteralfeeds.
Parenteral formulas containing glutamine or n-3 fatty acids are also available
commercially.
Individual components of immunonutrition have been reportedto
preserve or augment various aspects of cellular immune functionand
to modify the production of inflammatory mediators.15
Many clinical trials of immunonutrition in critically ill and
surgical patients have been performed that used various nutrient
combinations. Three meta-analyses give a fairly consistentview of
the clinical efficacy of enteral immunonutrition.68 All three considered only randomised controlled trials
in eithersurgical or critically ill patients; the control was a
"standard"enteral feed in all. Most trials used a combination of
arginine,n-3 fatty acids, and nucleotides, whereas some used a
combinationof these nutrients and glutamine and branched chain amino
acidsor of arginine and n-3 fatty acids. The experimental feedswere often much higher in total nitrogen content and contained
greater amounts of antioxidant vitamins and minerals such as vitamins A and E
and selenium.
All three meta-analyses found that immunonutrition results in
notable reductions in infections and in length of stay in hospital.
In general the reduced infection rate and length of hospitalstay are
more pronounced in surgical than critically ill patients.89 Despite these apparent benefits of immunonutrition,
noneof the meta-analyses identified a significant effect of
immunonutritionon mortality either across all trials considered or
withinsurgical or critically ill patients. It is this outcome thathas caused the greatest controversy and discussion.89 Thisis partly because one trial showed
significantly increasedmortality in critically ill patients
receiving immunonutrition,an effect that was more pronounced in
patients with sepsis.However, another study showed a reduction in
mortality in critically ill patients with sepsis receiving immunonutrition.10 Thiseffect was much more pronounced in
those patients who were lessill, and no advantage in survival was
seen in patients witha higher score.10
The reasons for the contradictory findingswith immunonutrition in
critically ill patients need to beunderstood more fully, and whether
these relate to the heterogeneousnature of this patient group or to
the presence or absence of specific nutrients within the immunonutrient mix
needs to beaddressed.
Trials have also shown some benefit from the "single" immunonutrientapproach. For example, enteral provision of glutamine decreased the
incidence of sepsis in premature neonates and the incidenceof
pneumonia, bacteraemia, and severe sepsis in criticallyill patients.2 However, in the latter study the decreased
rate of infection was not associated with decreased mortality.2 Parenteral glutamine decreased the incidence of
infections inrecipients of bone marrow transplantation and changed
the patternof mortality in patients in intensive care.2 These clinicalbenefits of glutamine seem to
be associated with improvements in intestinal integrity and in cellular immune
function.2
An enteral feed that differed in lipid composition from the
control (among other differences, it contained n-3 fatty acids,which
the control feed did not3) was shown to decrease
therequirement for supplemental oxygen, time on ventilation support,
and length of stay in the intensive care unit in patients with
moderate and severe acute respiratory distress syndrome.11Total length of stay in hospital and mortality also tendedto
be decreased in the treatment group, and fewer patientsdeveloped new
organ failure.11 Although several studies reportpotential immune benefits and anti-inflammatory effects of
parenteral n-3 fatty acids,36
few trials of the effect ofthis approach on clinical outcomes exist.
Recent trials using parenteral n-3 fatty acids in surgical patients show immunebenefits and anti-inflammatory effects12
but no reductionin infection rate or mortality, although
postoperative stayin intensive care and in hospital tended to be
shorter in thefish oil group.12
Trials of immunonutrients indicate several beneficial clinical
effects, particularly in surgical patients. However, doubtsremain
about the efficacy of this approach in critically illpatients, with
contradictory findings among trials. Methodologicaldifferences among
trials hamper comparisons.89
Use of immunonutrition should be approached cautiously in the most critically
ill patients.89 Future
efforts should try and define the mosteffective nutrients and
optimal mixes for use in differentpatient groups.
Philip C Calder, professor of nutritional immunology
Institute of Human Nutrition, School of Medicine, University
of Southampton, Southampton SO16 7PX (pcc@soton.ac.uk)
An overview of
nutrients with theirkey functions and effects appears on
bmj.com
Competing interests: PC has been reimbursed for attending orpaid a fee for speaking at conferences by Baxter Clintec, B
Braun, Danone, Fresenius, Nestle, Nuteral, and SHS Internationaland
has received research funding from Nutricia.
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This article has been cited by other articles:
D. J W Knight Immunonutrition: Increased mortality is associated with
immunonutrition in sepsis
BMJ, September 20, 2003; 327(7416): 682 - 683.
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